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XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells

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dc.contributor.author Hu, Chih-Chi Andrew
dc.contributor.author Dougan, Stephanie K.
dc.contributor.author McGehee, Annette M.
dc.contributor.author Love, J. Christopher
dc.contributor.author Ploegh, Hidde
dc.date.accessioned 2012-10-25T20:20:49Z
dc.date.available 2012-10-25T20:20:49Z
dc.date.issued 2009-04
dc.date.submitted 2009-02
dc.identifier.issn 0261-4189
dc.identifier.issn 1460-2075
dc.identifier.uri http://hdl.handle.net/1721.1/74263
dc.description.abstract XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of XBP-1 in B cells is a differentiation-dependent event, but not the result of a UPR caused by the abundant synthesis of secreted IgM. Without XBP-1, B cells fail to signal effectively through the B-cell receptor. The signalling defects lead to aberrant expression of the plasma cell transcription factors IRF4 and Blimp-1, and altered levels of activation-induced cytidine deaminase and sphingosine-1-phosphate receptor. Using XBP-1-deficient/Blimp-1-GFP transgenic mice, we find that XBP-1-deficient B cells form antibody-secreting plasmablasts in response to initial immunization; however, these plasmablasts respond ineffectively to CXCL12. They fail to colonize the bone marrow and do not sustain antibody production. These findings define the role of XBP-1 in normal plasma cell development and have implications for management of B-cell malignancies. en_US
dc.description.sponsorship National Science Foundation (U.S.). Graduate Research Fellowship Program en_US
dc.description.sponsorship Cancer Research Institute (New York, N.Y.) (Fellowship) en_US
dc.language.iso en_US
dc.publisher Nature Publishing Group en_US
dc.relation.isversionof http://dx.doi.org/10.1038/emboj.2009.117 en_US
dc.rights Creative Commons Attribution en_US
dc.rights.uri http://creativecommons.org/licenses/by/3.0/ en_US
dc.source PMC en_US
dc.title XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells en_US
dc.type Article en_US
dc.identifier.citation Hu, Chih-Chi Andrew et al. “XBP-1 Regulates Signal Transduction, Transcription Factors and Bone Marrow Colonization in B Cells.” The EMBO Journal 28.11 (2009): 1624–1636. © 2012 European Molecular Biology Organization en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Biology en_US
dc.contributor.department Whitehead Institute for Biomedical Research en_US
dc.contributor.department Massachusetts Institute of Technology. Department of Chemical Engineering en_US
dc.contributor.mitauthor Hu, Chih-Chi Andrew
dc.contributor.mitauthor Dougan, Stephanie K.
dc.contributor.mitauthor McGehee, Annette M.
dc.contributor.mitauthor Love, J. Christopher
dc.contributor.mitauthor Ploegh, Hidde
dc.relation.journal EMBO Journal en_US
dc.identifier.mitlicense PUBLISHER_CC en_US
dc.eprint.version Final published version en_US
dc.type.uri http://purl.org/eprint/type/JournalArticle en_US
eprint.status http://purl.org/eprint/status/PeerReviewed en_US
dspace.orderedauthors Hu, Chih-Chi Andrew; Dougan, Stephanie K; McGehee, Annette M; Love, J Christopher; Ploegh, Hidde L en


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